Platelet aggregation has been shown to be a consistent manifestation of endotoxin shock. It is possible that prostaglandin metabolism is altered by endotoxin as a mechanism for its effect on aggregation. Thromboxane A2, a potent aggregant, is synthesized in the platelet. In the blood vessel wall, a potent anti-aggregant, Prostaglandin I2, is formed. Both sites will be studied in order to determine the specific effect of the endotoxin molecule as well as that of endotoxemia on prostaglandin metabolism. A dose-response relationship will be established between endotoxin and platelet aggregation in dogs. Platelets from endotoxemic dogs will be studied to reveal their aggregation characteristics and prostaglandin (PG) synthesis. Synthesis of anti-aggregant PGI in endotoxemic vascular tissue will be assayed against aggregating platelets. In vitro studies will also be carried out to pharmacologically determine the site of action for endotoxin on Thromboxane synthesis in aggregating platelets and on Prostaglandin I synthesis in normal vascular tissue.